Transcutaneous electrical nerve stimulation (TENS) is a well known medical treatment used primarily for symptomatic relief and management of chronic intractable pain and as an adjunctive treatment in the management of post surgical and post traumatic acute pain. TENS involves the application of electrical pulses to the skin of a patient, which pulses are generally of a low frequency and are intended to affect the nervous system in such a way as to suppress the sensation of pain that would indicate acute or chronic injury or otherwise serve as a protective mechanism for the body. Typically, two electrodes are secured to the skin at appropriately selected locations. Mild electrical impulses are then passed into the skin through the electrodes to interact with the nerves lying thereunder. As a symptomatic treatment, TENS has proven to effectively reduce both chronic and acute pain of patients. However, TENS has shown no capacity for curing the causes of pain, rather the electrical energy simply interacts with the nervous system to suppress or relieve pain.
The human nervous system essentially serves as a communication system for the body wherein information concerning the state of the body is communicated to the spinal cord (and/or brain) and behavioral instructions are communicated from the brain (and/or spinal cord) to the rest of the body. Thus, there are ascending neural pathways, such as the ascending pain pathways, and descending neural pathways, such as the descending inhibitory pathway (DIP), within the nervous system.
Briefly, pain impulses received by the free nerve endings of nociceptive nerve fibers (in particular, A.delta. and C fibers) are conducted, through various synapses, to the brain. In particular, these first order neurons enter the dorsal horn of the spinal cord and synapse with second order neurons, which are either relay cells, projecting into the brain stem or thalamus, or interneurons, synapsing to other interneurons or to relay cells. The second order neurons then (mostly) cross the spinal cord and become the anterolateral system, comprised of the neospinothalamic tract (or lateral spinothalamic tract) and paleospinothalamic tract. The nerve fibers of the anterolateral system then terminate in various regions of the brain, including the brain stem, midbrain and thalamus.
Inhibition (or modulation) of pain, by the body, can occur anywhere from the point of origin of the pain through the successive synaptic junctions in the pain's central pathway. For example, following the descending inhibitory pathways (DIP) of pain inhibition/modulation, stimulation in the cerebral cortex of the brain descends to the thalamus and then to the periaqueductal gray (PAG) of the midbrain. The PAG region is rich in opiate receptors responsible for secreting morphine-like enkephalins and endorphins. Nerve fibers from the PAG then descend to the nucleus raphe magnus (NRM) in the brainstem. The NRM is responsible for the secretion of serotonin, a compound that is instrumental in elevating pain threshold levels and combating depression. Fibers from the NRM then descend into the spinal cord, synapsing with other inhibitory interneurons to cause secretion of additional powerful anti-pain neurotransmitters such as gamma-aminobutyric acid (GABA).
While prior art TENS devices and methods have been shown to be capable of affecting the ascending pathways of pain perception, they have shown little or no ability to affect the descending inhibitory pathways of the nervous system. The precise mechanisms by which these prior art TENS methods operate to affect pain are not known; however, one theory suggests that, by producing fast electrical waves that travel up the A.beta. nociceptive fibers, the TENS electrical stimulation pulses block pain stimulus traveling up the A.delta. and C fibers. One frequently reported problem with the prior art TENS methods is acclimation or accommodation; that is, the patient acclimates to the transcutaneous stimulation and the pain returns. The intensity of the treatment, in such cases, is increased to overcome the patient's accommodation of the treatment, but shortly, a maximum level of intensity is reached and further treatment is ineffective.
A TENS stimulator is, in effect, an electrical pulse generator which delivers electrical pulses (or impulses), transcutaneously, at a predetermined fixed or variable frequency. Typically, TENS stimulators deliver electrical pulses at frequencies in the range of about 50 to 200 Hertz (Hz). Most commonly, variable frequency TENS devices operate by beginning stimulation at the lowest frequency setting then increasing the frequency of stimulation until a pre-defined event occurs, such as motor nerve response or patient comfort achieved. Such increases in frequency may be controlled by a doctor or other medical personnel or, more often, are controlled by the patient him/herself. In addition to increasing the frequency of the stimulation pulses, the patient may be treated by simultaneously increasing the intensity (or amplitude) of the stimulation output of the device.
For example, the patient may have a choice of different "levels" of stimulation, each sequential level providing an increased frequency and intensity of stimulation as compared to the previous level. In either case, the output parameters generally start at their lowest level and are increased over the duration of the treatment.
Normally, when the patient (or other operator) increases the stimulation level of the TENS machine, in accordance with his/her doctor's instructions, the new, higher level is somewhat uncomfortable at first. However, as the patient knows from experience, his/her body accommodates to the new higher level of stimulation within a tolerable length of time. Once stimulation at one level becomes fully accommodated, that is, no longer works well to relieve the symptoms for which the treatment is being administered, the patient increases the stimulation level. Thus, as mentioned previously, the body is able to adjust to the electrical stimulation, requiring ever increasing levels of stimulation to achieve the same level of pain relief, often until no amount of stimulation is effective.
In some cases, the treatment frequency of the TENS device is fixed by design, or is established as a preselected, generally arbitrary, rate at the time of treatment, and only adjustment of the intensity (or amplitude) of the electrical pulses is allowed. The typical intensity level of TENS stimulators is in the range of 30-200 volts. The waveform characteristic of the electrical pulses varies and includes, for example, symmetrical sinusoidal waveforms, symmetrical biphasic waveforms and DC needle spikes. Generally, the different waveforms are believed to offer some advantage over other waveforms; however, there has been no clear consensus that any particular type of waveform is consistently more advantageous than other types. What is known, however, is the general shape of the action potential waveform that is responsible for producing electrical activity in neurons. Characteristic of this action potential are a very fast rise time and a slow decay.
The precise mechanisms by which transcutaneous electrical stimulation operates to control pain are not known. When used to treat pain, the patch electrodes of the TENS device are generally attached to the patient in the vicinity of the pain. Thus, for example, in treating joint pain, electrodes would be affixed near the joint and stimulation administered thereto. This localized stimulation then affects the nervous system to reduce the patient's perception of pain, presumably by either affecting the pain signals being sent from the region to the brain or by affecting the brain's perception of the signals it is receiving from the region. Even the body's natural mechanisms for perceiving and affecting pain are poorly understood. However, it is known that various biochemicals are released by nerve and brain cells in response to chemical and/or electrical stimulation of those cells. These neurotransmitters assist in the transmission of electrical messages between and within the peripheral and central nervous systems.
In contrast to the TENS devices and methods used to affect the ascending pathways of the nervous system, implantable electrical stimulators have been used to affect descending motor pathways of the nervous system. These electrical stimulators are surgically implanted into the patient's brain in order to affect, by direct electrical stimulation, specific regions of the brain. For example, by implantation of a stimulating electrode into the appropriate brain region, such as the thalamus and/or basal ganglia, nervous activity within the brain can be affected and the symptoms of movement disorders, such as akinesia, bradykinesia or rigidity and hyperkinetic disorders, can be reduced. See for example U.S. Pat. No. 5,716,377, Rise, et al., the entirety of which is hereby incorporated by reference. Thus, by stimulating the brain in this manner, the skeletal muscles at the termination of the descending motor pathway are affected. Obviously, surgical implantation of an electrode into the brain, as well as direct electrical stimulation of the brain are risky procedures that are preferably utilized only in the most extreme cases and after failure of less risky procedures.
Various disease conditions and disorders involve the brain and/or nervous system and thus may be amenable to treatment using drugs and/or electrical stimulation. For example, U.S. Pat. No. 5,716,377, issued to Rise, et al., Feb. 10, 1998, describes a method of treating movement disorders by means of an electrode implanted into the brain of the patient. Similarly, U.S. Pat. No. 5,713,923, issued to Ward, et al., Feb. 3, 1998, describes a method of treating epilepsy using a brain implanted electrode in combination with one or more drugs. While the effects of electrical stimulation of certain specific nerves, specific nerve/brain regions and/or specific muscles to treat different diseases and/or disorders have been described, few if any generalizations have resulted therefrom. That is, it is still very difficult to predict what if any type of nerve stimulation or drug therapy will work for any given disorder.
Essential tremor (E.T.) is a movement disorder afflicting more than 5 million people in the United States alone. This disease, which is the most common adult movement disorder, is about 20 times more prevalent than the tremors associated with Parkinson's Disease and is a poorly understood hereditary disorder. It is estimated that 32 in 1000 persons over the age of 60 years suffers from E.T. About 95% of those with this disease experience tremors, i.e. uncontrollable shaking, in both hands, often rendering the hands useless or near useless. Further, E.T. is the primary cause of head tremors (Titubation), which tremors are not only extremely difficult to treat but are particularly embarrassing and debilitating. In particularly severe cases, E.T. patients have elected to undergo difficult and dangerous brain surgery wherein the part of the brain responsible for the tremors is destroyed. Unfortunately, this surgery can result in the unintended permanent impairment or destruction (i.e., paralysis) of movement speech and/or swallowing functions as well as paraesthesia or tingling sensations in the patient's hands and/or head.
The current treatment of choice for essential tremor is drug therapy. However, an estimated 60% of E.T. patients do not respond to drug therapy and must therefore either live with the condition or resort to more dangerous and more invasive forms of treatment. Even when drug therapy is "successful," it rarely results in diminution of head tremors; rather, only hand tremors may respond to the therapy. Further, the patient's body usually acclimates to the drug therapy, requiring increased dosages of drugs, which, after time, become less effective. This necessitates frequent changes in drugs in order to obtain or maintain the same level of relief.
Prior to 1997, in the U.S.A., the only alternative to drug therapy for the relief of the symptoms of essential tremor was surgical destruction of part of the thalamus, from where the tremors are believed to originate. In 1997, (1995 in Europe), an implantable electronic stimulating device was approved for the treatment of essential tremor. This device is implanted deep into the thalamus of the patient and electrical stimulation of that brain structure is used to control the tremor. However, the device is effective to control tremors only unilaterally, that is in only one hand. Further, the success rate of the device is not great, particularly given the invasive nature of the procedure: with about 67% of 113 Parkinson's disease patients in one study experiencing control of tremors and about 58% of 83 essential tremor patients in the study being relieved. Because almost all essential tremor patients suffer bilateral tremors (tremors in both hands), those wishing to have the brain implant must choose which hand to control, at least unless and until more than one implant may be used simultaneously, a procedure that to date has not been approved. Also, the brain implant has no effect on titubation (head tremor).
A prior art implantable brain stimulation device is described for example in U.S. Pat. No. 5,716,377, issued to Rise, et al. and incorporated herein, in its entirety, by reference. This patent describes the use of an implantable device having the stimulating electrode implanted into the basal ganglia or thalamus of the patient, with the electrode lead passing under the skin of the patient to a pulse generator also implanted subcutaneously. Also described in the '377 patent, is the implantable device including a sensor for sensing the tremors. The sensor is also implanted and is connected to the pulse generator. The brain stimulation device is operated at 0.1 to 20 volts and at a frequency of between 2 to 2500 Hertz. Such devices are expensive, about $10,000 for the device plus about $25,000 for the required surgery, and require replacement of the pulse generator, and hence additional surgery and expense, about every three years.
Like essential tremor and Parkinson's disease, dementia disorders such as Alzheimer's disease are primarily diseases of the brain. Alzheimer's disease is a degenerative disease in which nerve cells within the brain die and their connections deteriorate. It is the most common cause of dementia and is the fourth leading cause of death among adults in the United States. While various causative factors have been postulated, such as heredity, environmental toxins and biochemical changes within the aging body, no specific cause for this disease had been identified.
Alzheimer's patients consistently have abnormally low levels of neurotransmitters in their brains, particularly a neurotransmitter known as acetylcholine. This reduction in neurotransmitters results in the gradual deterioration of the patient's mental processes and intellectual functioning, including memory loss, especially short-term memory, behavioral changes, inability to properly use language and the inability to perform skilled activities. Autopsies of Alzheimer's patients reveal the formation of protein plaques, comprised primarily of beta-amyloid protein, within the critical memory and learning centers of the brain. Studies on rats have demonstrated that injection of substance P can block the nerve damage caused by beta-amyloid, and thus, a significant portion of research efforts aimed at controlling this disease have focused on this and other brain biochemicals.
Presently, there is no cure or prevention for Alzheimer's disease. However, two different drugs have been approved in the United States for use in the management of this disease. While neither drug has been proven to provide long term relief from the degenerative process of Alzheimer's, at least one of the drugs has recently demonstrated an ability to stop the decline in memory and alertness for 84% of patients studied for a six month period. Further this drug, known as Aricept (produced by Eisai, a Japanese company), does not apparently cause the liver-toxic side effects seen with the other approved drug. Thus, research on drug therapies for the treatment of Alzheimer's disease continue.
Recently, the treatment of dementia disorders by electrical stimulation of specific cranial nerves has been described. U.S. Pat. No. 5,269,303, issued to Wernicke, et al., Dec. 14, 1993, describes stimulation of the vagus nerve to treat patients with dementia, and U.S. Pat. No. 5,540,734, issued to Zabara, Jul. 30, 1996, describes stimulation of one or both of the trigeminal and glossopharyngeal nerves to treat a variety of neurological, medical and psychiatric disorders, including dementia disorders. Each of these patents are hereby incorporated by reference in their entirety. Unfortunately, however, these methods are premised upon implantation of stimulation electrodes directly onto the specified nerve. This not only means that the patient must undergo major surgery to receive treatment, but also that the scope of treatment will be limited to the specific nerves upon which the electrode is implanted. Thus, once implanted, should the device not work to relieve the symptoms of the dementia or, worst, should the nerve stimulation result in intolerable side effects, either the device must be surgically explanted or must be deactivated and left within the patient's body.
Thus, what is needed is an inexpensive non-invasive method of treating neurology-related disorders, such as dementia disorders and/or movement disorders, that will be effective to relieve the very severe symptoms associated therewith. In particular, with respect to movement disorders, such as essential tremor and tremors associated with Parkinson's disease, methods of providing relief for both bilateral hand tremors and head tremors is needed. Similarly, with respect to dementia disorders, such as Alzheimer's disease, even a slowing of the deterioration associated with the disorders would be welcomed.